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Abstract
Background: Depression is a frequently encountered issue during pregnancy and postpartum. Both depression itself and the use of antidepressant medications can have implications for the infant's well-being. Studies have linked maternal depression to adverse outcomes like preterm birth, low birth weight, fetal growth restriction, and potential cognitive and emotional challenges for the child after birth. On the other hand, exposure to antidepressants during pregnancy has been associated with an increased risk of preterm birth, a decrease in birth weight, and congenital malformations.
Objectives: In light of these considerations, a scoping review was conducted to examine recent research findings concerning antidepressant use during pregnancy.
Methods: This study was a scoping review. Pubmed and Scopus databases were used to search for all relevant studies published from 2019 until 2023. Studies were excluded if they were case reports, narrative reviews, systematic reviews, or meta-analyses. Finally, all eligible articles were assessed for their outcomes.
Results: The use of SSRIs and duloxetine antidepressants in perinatal women was linked to preterm birth and smaller gestational sizes compared to controls, according to three cohort studies. Congenital malformation was also associated with duloxetine, mirtazapine, and atomoxetine use during pregnancy (3 cohort studies).
Conclusions: Recognizing the potential risks to the infant and the risk of leaving maternal depression untreated is crucial when making the decision to use antidepressants during pregnancy. This underscores the importance of a thoughtful and informed approach to managing depression in pregnant women.
Keywords: Antidepressant, drug safety, perinatal depression, pregnancy
Keywords
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References
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- Birth Outcomes: An Updated Systematic Review. Maternal and Child Health Journal, 19(6), 1306-1337. https://doi.org/10.1007/s10995-014-1637-2
- Ankarfeldt, M.Z., Petersen, J., Andersen, J.T., Fernandes, M.F.S., Li, H., Motsko, S.P., Fast, T., & Jimenez-Solem, E. (2023). Duloxetine Exposure During Pregnancy and the Risk of Offspring Being Born Small for Gestational Age or Prematurely: A Nationwide Danish and Swedish Safety Study. Drugs - Real World Outcomes, 10(1), 69–81. https://doi.org/10.1007/s40801-022-00334-2
- Ankarfeldt, M.Z., Petersen, J., Andersen, J.T., Li, H., Motsko, S.P., Fast, T., Hede, S.M., & Jimenez-
- Solem, E. (2021). Exposure To Duloxetine During Pregnancy and Risk of Congenital Malformations and Stillbirth: A Nationwide Cohort Study in Denmark and Sweden. PLoS Medicine, 18(11), 1–17. https://doi.org/10.1371/journal.pmed.1003851
- Bérard, A., Zhao, J.P., & Sheehy, O. (2017). Antidepressant Use During Pregnancy and The Risk of Major Congenital Malformations In A Cohort of Depressed Pregnant Women: An Updated Analysis of The Quebec Pregnancy Cohort. BMJ Open, 7(1), 1–13. https://doi.org/10.1136/bmjopen-2016-013372
- Bröms, G., Hernandez-Diaz, S., Huybrechts, K.F., Bateman, B.T., Kristiansen, E.B., Einarsdóttir, K., Engeland, A., Furu, K., Gissler, M., Karlsson, P., Klungsøyr, K., Lahesmaa-Korpinen, A.M., Mogun, H., Nørgaard, M., Reutfors, J., Sørensen, H.T., Zoega, H., & Kieler, H. (2023). Atomoxetine in Early Pregnancy and the Prevalence of Major Congenital Malformations: A Multinational Study. J.ournal of Clinical Psychiatry, 84(1), 1–12. https://doi.org/10.4088/JCP.22m14430
- Byatt, N., Deligiannidis, K.M., & Freeman, M.P. (2013). Antidepressant Use in Pregnancy: A Critical Review Focused on Risks and Controversies. Acta Psychiatrica Scandinavica, 127(2), 94–114. https://doi.org/10.1111/acps.12042
- Byrn, M.A. & Penckofer, S. (2013). Antenatal Depression and Gestational Diabetes: A Review of
- Maternal and Fetal Outcomes. Nursing for Women's Health, 17(1), 22–33. https://doi.org/10.1111/1751-486X.12003
- Cantarutti, A., Merlino, L., Monzani, E., Giaquinto, C., & Corrao, G. (2016). Is the Risk of Preterm Birth and Low Birth Weight Affected by the Use of Antidepressant Agents during Pregnancy? A Population-Based Investigation. PLoS One, 11(12), 1–10. https://doi.org/10.1371/journal.pone.0168115
- Ciesielski, T.H., Marsit, C.J., & Williams, S.M. (2015). Maternal Psychiatric Disease and Epigenetic Evidence Suggest A Common Biology For Poor Fetal Growth. BMC Pregnancy and Childbirth,15(192), 1–9. https://doi.org/10.1186/s12884-015-0627-8
- Furu, K., Kieler, H., Haglund, B., Engeland, A., Selmer, R., Stephansson, O., Valdimarsdottir, U.A.,
- Zoega, H., Artama, M., Gissler, M., Malm, H., & Nørgaard, M. (2015). Selective Serotonin Reuptake Inhibitors and Venlafaxine In Early Pregnancy and Risk of Birth Defects: Population Based Cohort Study and Sibling Design. BMJ (Online), 350, 1–9. https://doi.org/10.1136/bmj.h1798
- Goodman, S.H. (2007). Depression in Mothers, in: Annual Review of Clinical Psychology. pp. 107–135. https://doi.org/10.1146/annurev.clinpsy.3.022806.091401
- Grigoriadis, S., VonderPorten, E.H., Mamisashvili, L., Tomlinson, G., Dennis, C.-L., Koren, G.,
- Steiner, M., Mousmanis, P., Cheung, A., Radford, K., Martinovic, J., & Ross, L.E. (2013). The Impact of Maternal Depression During Pregnancy on Perinatal Outcomes: A Systematic Review and Meta-Analysis. The Journal of Clinical Psychiatry, 74(4), 321–341.
- Heinonen, E., Blennow, M., Blomdahl-Wetterholm, M., Hovstadius, M., Nasiell, J., Pohanka, A.,
- Gustafsson, L.L., & Wide, K. (2021). Sertraline Concentrations In Pregnant Women Are Steady and The Drug Transfer To Their Infants Is Low. European Journal of Clinical Pharmacology, 77(9), 1323–1331. https://doi.org/10.1007/s00228-021-03122-z
- Hoirisch-Clapauch, S., Brenner, B., & Nardi, A.E. (2015). Adverse Obstetric and Neonatal Outcomes In Women With Mental Disorders. Thrombosis Research, 135(Suppl.1), 560–563. https://doi.org/10.1016/S0049-3848(15)50446-5
- Huybrechts, K.F., Sanghani, R.S., Avorn, J., & Urato, A.C. (2014). Preterm Birth and
- Antidepressant Medication Use During Pregnancy: A Systematic Review and Meta-Analysis. PLoS One, 9(3), 1–13. https://doi.org/10.1371/journal.pone.0092778
- Kingston, D., Kehler, H., Austin, M.P., Mughal, M.K., Wajid, A., Vermeyden, L., Benzies, K., Brown, S., Stuart, S., & Giallo, R. (2018). Trajectories of Maternal Depressive Symptoms During Pregnancy and The First 12 Months Postpartum and Child Externalizing and Internalizing Behavior At Three Years. PLoS One, 13(4), 1–19. https://doi.org/10.1371/journal.pone.0195365
- Ostenfeld, A., Petersen, T.S., Pedersen, L.H., Westergaard, H.B., Løkkegaard, E.C.L., & Andersen,
- J.T. (2022). Mirtazapine Exposure In Pregnancy and Fetal Safety: A Nationwide Cohort Study. Acta Psychiatrica Scandinavica, 145(6), 557–567. https://doi.org/10.1111/acps.13431
- Räisänen, S., Lehto, S.M., Nielsen, H.S., Gissler, M., Kramer, M.R., & Heinonen, S. (2014). Risk Factors For and Perinatal Outcomes of Major Depression During Pregnancy: A Population-Based Analysis During 2002-2010 In Finland. BMJ Open, 4(11), 1–8. https://doi.org/10.1136/bmjopen-2014-004883
- Siu, A.L., Bibbins-Domingo, K., Grossman, D.C., Baumann, L.C., Davidson, K.W., Ebell, M., García,
- F.A.R., Gillman, M., Herzstein, J., Kemper, A.R., Krist, A.H., Kurth, A.E., Owens, D.K., Phillips, W.R., Phipps, M.G., & Pignone, M.P. (2016). Screening for Depression in Adults US Preventive Services Task Force Recommendation Statement. JAMA - Journal of The American Medical Association, 315(4), 380–387. https://doi.org/10.1001/jama.2015.18392
- Smit, M., Dolman, K.M., & Honig, A. (2016). Mirtazapine in Pregnancy and Lactation - A Systematic Review. European Neuropsychopharmacol, 26(1), 126–135. https://doi.org/10.1016/j.euroneuro.2015.06.014
- Sujan, A.C., Rickert, M.E., Quinn, P.D., Ludema, C., Wiggs, K.K., Larsson, H., Lichtenstein, P.,
- Almqvist, C., Öberg, A.S., & D’Onofrio, B.M. (2021). A Population-Based Study of Concurrent Prescriptions of Opioid Analgesic and Selective-Serotonin Reuptake Inhibitor Medications During Pregnancy and Risk For Adverse Birth Outcomes. Paediatric and Perinatal Epidemiology, 35(2), 184–193. https://doi.org/10.1111/ppe.12721
- Szegda, K., Markenson, G., Bertone-johnson, E.R., & Chasan-Taber, L. (2014). Depression During Pregnancy: A Risk Factor For Adverse Neonatal Outcomes? A Critical Review of The Literature. The Journal of Maternal-Fetal & Neonatal Med,icine 27(9), 960–967. https://doi.org/10.3109/14767058.2013.845157.Depression
- Underwood, L., Waldie, K., D’Souza, S., Peterson, E.R., & Morton, S. (2016). A Review of Longitudinal Studies On Antenatal and Postnatal Depression. Arch.ives of Women's Mental Health, 19, 711–720. https://doi.org/https://doi.org/10.1007/s00737-016-0629-1
- Vahia, V.N. (2013). Diagnostic and Statistical Manual of Mental Disorders 5: A Quick Glance.
- Indian Journal of Psychiatry, 55(3), 220–223. https://doi.org/10.4103/0019-5545.117131
- Van Niel, M.S. & Payne, J.L. (2020). Perinatal Depression: A Review. Cleveland Clinic Journal of Medicine, 87(5), 273–277. https://doi.org/10.3949/ccjm.87a.19054
- Vigod, S.N., Wilson, C.A., & Howard, L.M. (2016). Depression in Pregnancy. BMJ (Open),
- , 1–9. https://doi.org/10.1136/bmj.i1547
- Winterfeld, U., Klinger, G., Panchaud, A., Stephens, S., Arnon, J., Malm, H., Te Winkel, B., Clementi, M., Pistelli, A., Maňáková, E., Eleftheriou, G., Merlob, P., Kaplan, Y.C., Buclin, T., & Rothuizen, L.E. (2015). Pregnancy Outcome Following Maternal Exposure to Mirtazapine. Journal of Clinical Psychopharmacology, 35(3), 250–259. https://doi.org/10.1097/JCP.0000000000000309
- Woolhouse, H., Gartland, D., Mensah, F., & Brown, S.J. (2014). Maternal Depression From Early Pregnancy To 4 Years Postpartum In A Prospective Pregnancy Cohort Study: Implications For Primary Health Care. BJOG: An International Journal of Obstetrics and Gynaecology, 122(3), 312–321. https://doi.org/10.1111/1471-0528.12837
- Zeszutek, S. (2021). Chapter 41 - Antidepressant Use In Pregnancy, in: Sidhartha D. Ray (Ed.),
- Side Effects of Drugs Annual. Elsevier, pp. 503–512. https://doi.org/https://doi.org/10.1016/bs.seda.2021.09.009
References
Accortt, E.E., Cheadle, A.C.D., & Dunkel Schetter, C. (2015). Prenatal Depression and Adverse
Birth Outcomes: An Updated Systematic Review. Maternal and Child Health Journal, 19(6), 1306-1337. https://doi.org/10.1007/s10995-014-1637-2
Ankarfeldt, M.Z., Petersen, J., Andersen, J.T., Fernandes, M.F.S., Li, H., Motsko, S.P., Fast, T., & Jimenez-Solem, E. (2023). Duloxetine Exposure During Pregnancy and the Risk of Offspring Being Born Small for Gestational Age or Prematurely: A Nationwide Danish and Swedish Safety Study. Drugs - Real World Outcomes, 10(1), 69–81. https://doi.org/10.1007/s40801-022-00334-2
Ankarfeldt, M.Z., Petersen, J., Andersen, J.T., Li, H., Motsko, S.P., Fast, T., Hede, S.M., & Jimenez-
Solem, E. (2021). Exposure To Duloxetine During Pregnancy and Risk of Congenital Malformations and Stillbirth: A Nationwide Cohort Study in Denmark and Sweden. PLoS Medicine, 18(11), 1–17. https://doi.org/10.1371/journal.pmed.1003851
Bérard, A., Zhao, J.P., & Sheehy, O. (2017). Antidepressant Use During Pregnancy and The Risk of Major Congenital Malformations In A Cohort of Depressed Pregnant Women: An Updated Analysis of The Quebec Pregnancy Cohort. BMJ Open, 7(1), 1–13. https://doi.org/10.1136/bmjopen-2016-013372
Bröms, G., Hernandez-Diaz, S., Huybrechts, K.F., Bateman, B.T., Kristiansen, E.B., Einarsdóttir, K., Engeland, A., Furu, K., Gissler, M., Karlsson, P., Klungsøyr, K., Lahesmaa-Korpinen, A.M., Mogun, H., Nørgaard, M., Reutfors, J., Sørensen, H.T., Zoega, H., & Kieler, H. (2023). Atomoxetine in Early Pregnancy and the Prevalence of Major Congenital Malformations: A Multinational Study. J.ournal of Clinical Psychiatry, 84(1), 1–12. https://doi.org/10.4088/JCP.22m14430
Byatt, N., Deligiannidis, K.M., & Freeman, M.P. (2013). Antidepressant Use in Pregnancy: A Critical Review Focused on Risks and Controversies. Acta Psychiatrica Scandinavica, 127(2), 94–114. https://doi.org/10.1111/acps.12042
Byrn, M.A. & Penckofer, S. (2013). Antenatal Depression and Gestational Diabetes: A Review of
Maternal and Fetal Outcomes. Nursing for Women's Health, 17(1), 22–33. https://doi.org/10.1111/1751-486X.12003
Cantarutti, A., Merlino, L., Monzani, E., Giaquinto, C., & Corrao, G. (2016). Is the Risk of Preterm Birth and Low Birth Weight Affected by the Use of Antidepressant Agents during Pregnancy? A Population-Based Investigation. PLoS One, 11(12), 1–10. https://doi.org/10.1371/journal.pone.0168115
Ciesielski, T.H., Marsit, C.J., & Williams, S.M. (2015). Maternal Psychiatric Disease and Epigenetic Evidence Suggest A Common Biology For Poor Fetal Growth. BMC Pregnancy and Childbirth,15(192), 1–9. https://doi.org/10.1186/s12884-015-0627-8
Furu, K., Kieler, H., Haglund, B., Engeland, A., Selmer, R., Stephansson, O., Valdimarsdottir, U.A.,
Zoega, H., Artama, M., Gissler, M., Malm, H., & Nørgaard, M. (2015). Selective Serotonin Reuptake Inhibitors and Venlafaxine In Early Pregnancy and Risk of Birth Defects: Population Based Cohort Study and Sibling Design. BMJ (Online), 350, 1–9. https://doi.org/10.1136/bmj.h1798
Goodman, S.H. (2007). Depression in Mothers, in: Annual Review of Clinical Psychology. pp. 107–135. https://doi.org/10.1146/annurev.clinpsy.3.022806.091401
Grigoriadis, S., VonderPorten, E.H., Mamisashvili, L., Tomlinson, G., Dennis, C.-L., Koren, G.,
Steiner, M., Mousmanis, P., Cheung, A., Radford, K., Martinovic, J., & Ross, L.E. (2013). The Impact of Maternal Depression During Pregnancy on Perinatal Outcomes: A Systematic Review and Meta-Analysis. The Journal of Clinical Psychiatry, 74(4), 321–341.
Heinonen, E., Blennow, M., Blomdahl-Wetterholm, M., Hovstadius, M., Nasiell, J., Pohanka, A.,
Gustafsson, L.L., & Wide, K. (2021). Sertraline Concentrations In Pregnant Women Are Steady and The Drug Transfer To Their Infants Is Low. European Journal of Clinical Pharmacology, 77(9), 1323–1331. https://doi.org/10.1007/s00228-021-03122-z
Hoirisch-Clapauch, S., Brenner, B., & Nardi, A.E. (2015). Adverse Obstetric and Neonatal Outcomes In Women With Mental Disorders. Thrombosis Research, 135(Suppl.1), 560–563. https://doi.org/10.1016/S0049-3848(15)50446-5
Huybrechts, K.F., Sanghani, R.S., Avorn, J., & Urato, A.C. (2014). Preterm Birth and
Antidepressant Medication Use During Pregnancy: A Systematic Review and Meta-Analysis. PLoS One, 9(3), 1–13. https://doi.org/10.1371/journal.pone.0092778
Kingston, D., Kehler, H., Austin, M.P., Mughal, M.K., Wajid, A., Vermeyden, L., Benzies, K., Brown, S., Stuart, S., & Giallo, R. (2018). Trajectories of Maternal Depressive Symptoms During Pregnancy and The First 12 Months Postpartum and Child Externalizing and Internalizing Behavior At Three Years. PLoS One, 13(4), 1–19. https://doi.org/10.1371/journal.pone.0195365
Ostenfeld, A., Petersen, T.S., Pedersen, L.H., Westergaard, H.B., Løkkegaard, E.C.L., & Andersen,
J.T. (2022). Mirtazapine Exposure In Pregnancy and Fetal Safety: A Nationwide Cohort Study. Acta Psychiatrica Scandinavica, 145(6), 557–567. https://doi.org/10.1111/acps.13431
Räisänen, S., Lehto, S.M., Nielsen, H.S., Gissler, M., Kramer, M.R., & Heinonen, S. (2014). Risk Factors For and Perinatal Outcomes of Major Depression During Pregnancy: A Population-Based Analysis During 2002-2010 In Finland. BMJ Open, 4(11), 1–8. https://doi.org/10.1136/bmjopen-2014-004883
Siu, A.L., Bibbins-Domingo, K., Grossman, D.C., Baumann, L.C., Davidson, K.W., Ebell, M., García,
F.A.R., Gillman, M., Herzstein, J., Kemper, A.R., Krist, A.H., Kurth, A.E., Owens, D.K., Phillips, W.R., Phipps, M.G., & Pignone, M.P. (2016). Screening for Depression in Adults US Preventive Services Task Force Recommendation Statement. JAMA - Journal of The American Medical Association, 315(4), 380–387. https://doi.org/10.1001/jama.2015.18392
Smit, M., Dolman, K.M., & Honig, A. (2016). Mirtazapine in Pregnancy and Lactation - A Systematic Review. European Neuropsychopharmacol, 26(1), 126–135. https://doi.org/10.1016/j.euroneuro.2015.06.014
Sujan, A.C., Rickert, M.E., Quinn, P.D., Ludema, C., Wiggs, K.K., Larsson, H., Lichtenstein, P.,
Almqvist, C., Öberg, A.S., & D’Onofrio, B.M. (2021). A Population-Based Study of Concurrent Prescriptions of Opioid Analgesic and Selective-Serotonin Reuptake Inhibitor Medications During Pregnancy and Risk For Adverse Birth Outcomes. Paediatric and Perinatal Epidemiology, 35(2), 184–193. https://doi.org/10.1111/ppe.12721
Szegda, K., Markenson, G., Bertone-johnson, E.R., & Chasan-Taber, L. (2014). Depression During Pregnancy: A Risk Factor For Adverse Neonatal Outcomes? A Critical Review of The Literature. The Journal of Maternal-Fetal & Neonatal Med,icine 27(9), 960–967. https://doi.org/10.3109/14767058.2013.845157.Depression
Underwood, L., Waldie, K., D’Souza, S., Peterson, E.R., & Morton, S. (2016). A Review of Longitudinal Studies On Antenatal and Postnatal Depression. Arch.ives of Women's Mental Health, 19, 711–720. https://doi.org/https://doi.org/10.1007/s00737-016-0629-1
Vahia, V.N. (2013). Diagnostic and Statistical Manual of Mental Disorders 5: A Quick Glance.
Indian Journal of Psychiatry, 55(3), 220–223. https://doi.org/10.4103/0019-5545.117131
Van Niel, M.S. & Payne, J.L. (2020). Perinatal Depression: A Review. Cleveland Clinic Journal of Medicine, 87(5), 273–277. https://doi.org/10.3949/ccjm.87a.19054
Vigod, S.N., Wilson, C.A., & Howard, L.M. (2016). Depression in Pregnancy. BMJ (Open),
, 1–9. https://doi.org/10.1136/bmj.i1547
Winterfeld, U., Klinger, G., Panchaud, A., Stephens, S., Arnon, J., Malm, H., Te Winkel, B., Clementi, M., Pistelli, A., Maňáková, E., Eleftheriou, G., Merlob, P., Kaplan, Y.C., Buclin, T., & Rothuizen, L.E. (2015). Pregnancy Outcome Following Maternal Exposure to Mirtazapine. Journal of Clinical Psychopharmacology, 35(3), 250–259. https://doi.org/10.1097/JCP.0000000000000309
Woolhouse, H., Gartland, D., Mensah, F., & Brown, S.J. (2014). Maternal Depression From Early Pregnancy To 4 Years Postpartum In A Prospective Pregnancy Cohort Study: Implications For Primary Health Care. BJOG: An International Journal of Obstetrics and Gynaecology, 122(3), 312–321. https://doi.org/10.1111/1471-0528.12837
Zeszutek, S. (2021). Chapter 41 - Antidepressant Use In Pregnancy, in: Sidhartha D. Ray (Ed.),
Side Effects of Drugs Annual. Elsevier, pp. 503–512. https://doi.org/https://doi.org/10.1016/bs.seda.2021.09.009